The cause of sickle cell crisis is unknown. Our preliminary studies have indicated a decreasing susceptibility of erythrocytes of sickle cell patients to sickle with recovery from crises episodes. Upon de-oxygenation the rate of sickling decreases. The ultimate percentage of sickled cells upon complete de-oxygenation remains the same. These observations are based on counting %SC in wet preparations. Work is now in progress in correlating these findings with objective measurements of filterability, viscosity, potassium loss and metabolic intracellular aspects in serial estimation of RBC samples of sickle cell disease patients during crises recovery and symptom free states. Preliminary observations show a good correlation between filterability changes and decreasing rate of sickling. With recovery we also do observe a rise in ATP and 2,3-DPG levels. In the symptom free state patients with mild disease (less than 4 crises episodes per year) show a higher level of 2,3-DPG and ATP when compared to patients with severe disease (more than 4 crises episodes per year).